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Disease-modifying therapies alter gut microbial composition in MS.

Ilana Katz Sand1, Yunjiao Zhu1, Achilles Ntranos1

  • 1Department of Neurology (I.K.S., A.N., R.B., Y.B.), Department of Neuroscience (Y.Z., P.C.), and Department of Genetics & Genomic Sciences, Icahn Institute for Genomics & Multiscale Biology (J.C.C.), Icahn School of Medicine at Mount Sinai; Department of Neurology (E.C., E.C.-H., S.S., B.A.C.C., S.E.B.), Weill Institute for Neurosciences, University of California, San Francisco; E.C. is now with Universities Space Research Association, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA; Department of Pediatrics (J.D., R.K.), Department of Computer Science & Engineering (R.K.), and Center for Microbiome Innovation (R.K.), University of California, San Diego; and Neuroscience Initiative (P.C.), Advanced Research Science Center at the Graduate Center of the City University of New York.

Neurology(R) Neuroimmunology & Neuroinflammation
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Summary

Disease-modifying therapies like glatiramer acetate (GA) and dimethyl fumarate (DMF) alter gut microbiota in multiple sclerosis (MS) patients. These changes impact key metabolic pathways, suggesting new therapeutic avenues for MS.

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Area of Science:

  • Microbiome research
  • Immunology
  • Neurology

Background:

  • Gut microbiota composition is increasingly recognized as a factor in immune system regulation.
  • Alterations in gut bacteria have been implicated in the pathophysiology of various autoimmune diseases, including multiple sclerosis (MS).
  • Disease-modifying therapies (DMTs) are standard treatments for MS, but their impact on the gut microbiome is not fully understood.

Purpose of the Study:

  • To investigate the effects of glatiramer acetate (GA) and dimethyl fumarate (DMF) on the gut microbial composition in patients with relapsing MS.
  • To identify specific bacterial taxa and functional pathways affected by these DMTs.

Main Methods:

  • 16S rRNA gene sequencing was performed on fecal DNA from treatment-naive MS patients and those treated with GA or DMF.
  • Operational Taxonomic Units (OTUs) were clustered using the GreenGenes database.
  • Differential abundance and functional pathway analyses were conducted using established bioinformatics tools.

Main Results:

  • Both GA and DMF treatments were associated with significant alterations in fecal microbiota composition compared to treatment-naive individuals.
  • Specific bacterial families, Lachnospiraceae and Veillonellaceae, showed decreased abundance with both GA and DMF.
  • Dimethyl fumarate (DMF) was further associated with decreased Firmicutes and Fusobacteria, and increased Bacteroidetes, while both therapies affected overlapping functional pathways.

Conclusions:

  • Glatiramer acetate (GA) and dimethyl fumarate (DMF) administration significantly modifies the gut microbial landscape in MS patients.
  • The observed changes in microbial composition and associated metabolic pathways may offer insights into MS pathophysiology.
  • These findings suggest potential mechanisms underlying DMT efficacy and highlight the gut microbiome as a target for future therapeutic interventions in MS.